Korean Chemical Engineering Research

The Korean Institute of Chemical Engineers (한국화학공학회)
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Layered Double Hydroxide Nanoparticles for Bio-Imaging Applications

LDH 나노입자 기반의 바이오 이미징 소재

  • Jin, Wenji (Department of Nano Materials Science and Engineering, Kyungnam University) ;
  • Ha, Seongjin (Department of Nano Materials Science and Engineering, Kyungnam University) ;
  • Lee, Dongki (Department of Nano Materials Science and Engineering, Kyungnam University) ;
  • Park, Dae-Hwan (Department of Nano Materials Science and Engineering, Kyungnam University)
  • 김문희 (경남대학교 나노신소재공학과) ;
  • 하성진 (경남대학교 나노신소재공학과) ;
  • 이동기 (경남대학교 나노신소재공학과) ;
  • 박대환 (경남대학교 나노신소재공학과)
  • Received : 2019.03.01
  • Accepted : 2019.04.10
  • Published : 2019.08.01
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Abstract

Layered double hydroxides (LDHs) nanoparticles have emerged as novel nanomaterials for bio-imaging applications due to its unique layered structure, physicochemical properties, and good biocompatibility. Bio-imaging is one of the most important fields for medical applications in clinical diagnostics and therapeutics of various diseases. Enhanced diagnostic techniques are needed to realize new paradigm for next-generation personalized medicine through nanoscale materials. When nanotechnology is introduced into bio-imaging system, nanoparticle probes can endow imaging techniques with enhanced ability to obtain information about biological system at the molecular level. In this review, we summarize structural features of LDH nanoparticles with current issues of bio-imaging system. LDH nanoparticle probes are also discussed through in vitro as well as in vivo studies in various bio-imaging techniques including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and computed X-ray tomography (CT), which will have the potential in the development of the advanced nanoparticles with high sensitivity and selectivity.

Layered double hydroxides (LDHs) 나노입자는 특유의 층상형 결정구조에서 기인된 물리화학적 물성 및 생체친화성을 바탕으로 나노-바이오 분야에서 주목을 받고 있다. 바이오 이미징은 질병의 진단과 치료(테라노스틱스, theranostics=therapy+diagnosis)에 다양하게 활용될 수 있는 핵심적인 분야로 차세대 맞춤의학으로의 새로운 패러다임 실현을 위해서 보다 정확하고 빠른 진단기술이 절실히 요구되고 있다. 이를 실현하기 위한 대안으로 나노기술이 접목된 고감도 분자영상 관련 연구들이 활발히 진행되고 있다. 본 총설에서는 LDH 나노입자를 기반으로 하는 바이오 이미징 시스템의 개발동향에 관하여 소개하고 바이오 이미징에 적합한 나노소재의 구조 및 합성 방법에 대하여 설명하였다. 또한 임상 의학에서 현재 많이 사용되고 있는 형광을 이용한 광학영상, 자기공명영상(MRI), 핵의학영상(PET), 컴퓨터 단층 촬영(CT) 등 다양한 분야에서 어떻게 LDH 나노입자를 이용하여 나노 프로브 개발을 할 수 있는지 연구사례를 기술하면서 나노기술과 첨단영상기술이 융합된 획기적인 고감도 나노 바이오 이미징 시스템 개발 및 그 잠재력에 대하여 전망해 보았다.

Keywords

HHGHHL_2019_v57n4_445_f0001.png 이미지

Fig. 1. Overview of layered double hydroxide nanoparticles and their related application systems. A. Fluorescence imaging, reproduced from [30,17], B. magnetic resonance imaging (MRI), reproduced from [15,35], C. positron emission tomography (PET), reproduced from [16], D. computerized tomography

HHGHHL_2019_v57n4_445_f0002.png 이미지

Fig. 2. Intracellular trafficking pathway of the LDH nanoparticles with a size of A. 50 nm and B. 100 nm: (a) schematic diagram of endocytic and exocytic pathways, (b) confocal microscopic images of the HOS cells treated with LDH-FITC (green) of 50 and 100 nm co-localized (yellowish) in specific organelles (red), early endosome, lysosome, and Golgi apparatus at 0.5 and 4 h, respectively, reproduced from [26]. C. (a) Intracellular trafficking pathway of active bio-LDHFA nanoparticles, (b) SEM image and size distribution of LDHFA/siSurvivin, (c) optic and fluorescence images of LDHFA-FITC/siSurvivin, reproduced from [33].

HHGHHL_2019_v57n4_445_f0003.png 이미지

Fig. 3. A. SEM imaging for Gd-DTPA/LDH, schematic of possible configuration and interactions between [Gd(DTPA)]2- and the positive hydroxide layer (inset image). B. The relaxation time (T1) map for (a) OmniscanTM (L: 2.87 mg/mL, R: 0.287 mg/mL), (b) Gd-DTPA/LDH (L: 1.14 mg/mL, R: 0.114 mg/mL), (c) saline, reproduced from [38,43].

HHGHHL_2019_v57n4_445_f0004.png 이미지

Fig. 4. A. Schematic illustration of synthetic procedure, B. (a) TEM image, (b) STEM image, C. structure related multifunctional properties of Mn-LDH nanoparticles, reproduced from [34].

HHGHHL_2019_v57n4_445_f0005.png 이미지

Fig. 5. A. Shematic illustration of MLDH and DOX&ICG/MLDH. B. (a) STEM image of MLDH nanosheets with corresponding EDX mapping images for Mg, Al and Gd, respectively, (b) HRTEM image of DOX&ICG/MLDH. C. In vivo T1-weighted MR images of the tumor bearing mice at different time points after i.v. injection of DOX&ICG/MLDH (tumors are indicated by the orange arrows), reproduced from [27].

HHGHHL_2019_v57n4_445_f0006.png 이미지

Fig. 6. A. Schematic illustration, TEM images and corresponding energy dispersive spectroscopy (EDS) mapping images of pristine LDH (a, a1, a2) and Co2+-substituted LDH (b, b1, b2) in 0.02 M Co2+ solution under 150 ℃ hydrothermal conditions. (Legend: yellow=Mg2+, cyan=Al3+, magenta=Co2+.) Reproduced from [42]. B. (a) TEM image of LDH nanoparticles, (b) LDH aggregated but LDHBSA remained stable after incubating LDH and LDH-BSA (4.7 mg/mL) in PBS for 7 days, (c) autoradiographic images of TLC plates of LDH, LDH-BSA and BSA after chelator-free labeling with 64Cu, (d) In vivo PET imaging. Serial coronal PET images at different time points post-injection of 64CuLDH-BSA were acquired in 4T1 tumor-bearing mice. Reproduced from [16].

HHGHHL_2019_v57n4_445_f0007.png 이미지

Fig. 7. A. SEM images of (a) LDH-Gd, (b) LDH-Gd/Au, B. shematic illustration of LDH-Gd/Au, C. CT images and D. CT value (HU) plots of aqueous solutions of iobitridol and LDH-Gd/Au at different concentrations, E. In vivo CT imaging of Kunming mice after intravenous injection of LDH-Gd/Au solution for different time periods (3D volume Rendering CT images), F. CT images of tumor after intravenous injection LDH-Gd/Au-heparin (dosage: 72.4 mg Au/kg) in 4T1 murine breast tumor-bearing mice for 0 h, 1 h and 4 h, reproduced from [35].

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